Embryonic morphogenesis, and development of the head and neck in particular, is the result of sophisticated cellular migrations which form virtually all of the skeletal, muscular and glandular structures. The mechanisms that underlie these cell migrations are poorly understood, despite the fact that they are responsible for many common congenital malformations. Recently, we have identified a novel enzymatic mechanism for mesenchymal cell migration on basal lamina substrates. Results suggest that cell surface galactosyltransferase (GalTase) recognizes and binds its appropriate substrates in the basal lamina facilitating cell:substrate adhesion and subsequent migration. Cell migration can be inhibited or stimulated with reagents that selectively inhibit or stimulate, respectively, surface GalTase activity. Interestingly, these reagents have no effect on cell migration on fibronectin substrates, showing substrate specificity of GalTase action. In this proposal, we will define the receptor function of surface GalTase during migration and identify its complementary ligand in the basal lamina. To accomplish these studies, we will examine the effects of monospecific anti-GalTase IgG on cell migration in vitro on a variety of defined substrates. Experiments will define the localization., turnover and recycling of surface GalTase during migration, as well as its relationship to the cytoskeleton. Anti-GalTase IgG will be injected into the migratory pathway of cranial neural crest cells to perturb craniofacial morphogenesis in vivo. The GalTase substrates in the basal lamina will be identified by conventional biochemical techniques. Migration will be analyzed on inert substrates derivatized with purified GalTase substrates that have been enzymatically modified. Since the surface GalTase appears to recognize laminin, we will examine the relationship between GalTase and the laminin receptor. As an independent screen, cell:matrix interactions will be identified with photoactivated heterobifunctional crosslinkers. Finally, we will attempt to correct the lethal migration-deficient T/T mutation in vitro and in vivo by inhibiting the excess surface GalTase activity down to normal levels. These results will enable us to define a specific molecular mechanism for some cell:matrix interactions during morphogenesis and will aid in our understanding of congenital malformations.